Acceleration of Lipid Peroxidation in α-Tocopherol Transfer Protein-Knockout Mice Following the Consumption of Drinking Water Containing a Radical Initiator
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概要
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To assess the antioxidative role of vitamin E (VE) in a mouse model of severe VE deficiency by using biomarkers, α-tocopherol transfer protein (α-TTP-/-)-knockout mice were maintained on a VE-deficient diet for 28 weeks [KO group, n = 6]. Wild-type C57BL/6 mice were maintained on a diet containing 0.002% α-tocopherol [WT group, n = 6]. The animals were housed individually in a metabolic cage from the age of 9 weeks (Week 0) to 27 weeks. Urine was collected every week, and the levels of total hydroxyoctadecadienoic acid (tHODE), 7-hydroxycholesterol (t7-OHCh), and 8-iso-prostaglandin F2α(t8-isoPGF2α), which are biomarkers for lipid peroxidation, were measured by gas chromatography (GC)-mass spectrometry. From the age of 21 weeks (Week 12), three mice in each group were provided drinking water containing the water-soluble radical initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) until the end of the study (Week 19). Blood and tissue samples were collected, and the levels of the abovementioned biomarkers therein were assessed. AIPH consumption clearly elevated the plasma and erythrocyte levels of tHODE and t8-isoPGF2α in both the WT and KO groups except for the erythrocyte level of tHODE in the WT group. Furthermore, this elevation was more prominent in the KO group than in the WT group. Interestingly, AIPH consumption reduced the stereoisomer ratio of HODE (ZE/EE), which is reflective of the efficacy of a compound as an antioxidant in vivo; this suggests that free radical-mediated oxidation reduces the antioxidant capacity in vivo. The urine levels of tHODE, t7-OHCh, and t8-isoPGF2α tended to increase with AIPH consumption, but these individual levels fluctuated. It was clearly demonstrated by the proposed biomarkers that maintaining α-TTP-/- mice on a VE-deficient diet results in a severe VE deficiency and promotes lipid peroxidation.
- 日本油化学会の論文
著者
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Hayakawa Mieko
Health Technology Research Center, National Institute of Advanced Industrial Science and Technology
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Yoshida Yasukazu
Health Technology Research Center National Institute Of Advanced Industrial Science And Technology (
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Yoshida Yasukazu
徳島大学医学部
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Niki Etsuo
Health Research Institute National Institute Of Advanced Industrial Science And Technology
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Cynshi Osamu
Fujigotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd.
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Jishage Kou-ichi
Fujigotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd.
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Yoshida Yasukazu
Health Research Institute National Institute Of Advanced Industrial Science And Technology
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Hayakawa Mieko
Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST)
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